Photoreceptor cells in the retina are sensory neurons that convert light signals into neuronal signals via phototransduction, a process that initiates visual senses. Phototransduction occurs in photoreceptors in specialized organelles, the outer segments. Loss of photoreceptors can lead to vision loss. This is especially prevalent in patients with hereditary retinal degenerations such as retinitis pigmentosa (RP), which affects over 100,000 Americans. Mutations in close to 60 genes are responsible for RP. Loss of vision is not only a personal tragedy but also a burden to the society. It is estimated that an RP patient has an average health care cost of $7,000 annually.
Rhodopsin, the photosensitive molecule that absorbs photons and initiates phototransduction, is densely packed in the outer segments of rod photoreceptors. Rhodopsin has intrinsic absorbance in the visible spectrum in the dark adapted state. When exposed to light, the absorption spectrum of rhodopsin undergoes a dramatic shift. Thus, rhodopsin is a functional biomarker for rod photoreceptors and, by imaging rhodopsin, the function of photoreceptors can be assessed.
The light-induced shift in rhodopsin absorption spectrum has been explored to assess the concentration of rhodopsin, thus of photoreceptors, in vivo. Fundus reflection densitometry, which measures the difference in rhodopsin light absorption in the dark- and light-adapted states, was developed to quantitatively assess rhodopsin in the retina. The first experimental setup based on fundus reflectometry was developed in the 1950s and was improved thereafter.
Early imaging techniques for fundus densitometry used fundus photographs on film, and later used, for example, video-based fundus reflectometers, scanning laser ophthalmoscopes (SLO), and charged-couple device (CCD) based fundus cameras. Currently, optical coherence tomography (OCT), SLO, and fundus photography are the major imaging techniques used for imaging the retinal structures. To date, however, little progress has been made in assessing quantitatively, via means of optical imaging, the function and structure of photoreceptors in vivo, which could provide crucial information for the diagnosis and monitoring of retinal degenerative disorders.